Flow cells have been constructed for liquid-phase measurements using fluorescent-based devices that require the sensor surface to be in contact with the environment. These flow cells are primarily designed to enhance the sensing characteristics of a particular component by blocking background light from influencing the sensor response. The device enclosure is constructed in a way to limit background light, a primary noise factor in fluorescent applications. Because the primary purpose of the cell is to control coupled light, the cell does not take into account rigid support for the optical fiber or additional processing needs such as mode stripping. In addition, flow cells have configurations that require external pumps or other methods to bring the external environment to the sensor as opposed to directly exposing the sensor to the external environment.
Crotts et al. (U.S. Pat. No. 6,215,943 B1) describe an optical fiber holder that allows a sample to be tested while avoiding strain and bending influences. The holder comprises a tube having a longitudinal axis, a first end for receiving an optical fiber and a recessed second end for protecting the optical fiber tip. An aperture is disposed along a length of the longitudinal axis of the tube for exposing the optical fiber to a sample. A change in a sample is determined by disposing an optical fiber device having a sensing element into the optical fiber holder. The optical fiber holder is then inserted into a vessel containing a sample and the sample is circulated past the sensing element. The problem with this device is that it requires that a large enough sample volume be available to submerge the device and to circulate the sample past the sensor. Therefore, small (microliter) samples cannot be used. In addition, there is no way to control the manner by which the sample contacts the sensor. This is of particular importance when one desires to conduct kinetic studies. Kinetic studies and studies where it is desirable to obtain results in real-time as various samples come into contact with one another are difficult to conduct with this device because the method of dipping is limited by diffusion. Moreover, this configuration is only applicable to large sample sizes. When sample sizes are on the microliter scale, the holder is reduced dimensionally and loses its structural rigidity and, hence, its capability to measure adequately.
Malmqvist et al. (U.S. Pat. No. 6,200,814 B1) provides a method and device for controlling a fluid flow over a sensing surface within a flow cell. The methods employ laminar flow techniques to position a fluid flow over one or more discrete sensing areas on the sensing surface of the flow cell. Such methods permit selective sensitization of the discrete sensing areas, and provide selective contact of the discrete sensing areas with a sample fluid flow. The method requires that the surface of the sensor be sensitized by activating the sensing surface such that it is capable of specifically interacting with a desired analyte. The sensor device comprises a flow cell having an inlet end and an outlet end; at least one sensing surface on a wall surface within the flow cell located between the inlet and outlet ends; wherein the flow cell has at least two inlet openings at the inlet end, and at least one outlet opening at the outlet end, such that separate laminar fluid flows entering the flow cell through the respective inlet openings can flow side by side through the flow cell and contact the sensing surface. In this aspect, the flow cell and the sensing surface are one in the same. In another aspect of the invention, the sensor system comprises a flow cell having an inlet end and an outlet end; at least one sensing area on a sensing surface within the flow cell between the inlet and outlet ends; the flow cell having at least two inlet openings at the inlet end, and at least one outlet opening at the outlet end; means for applying laminar fluid flows through the inlet opening such that the laminar fluid flows pass side by side through the flow cell over the sensing surface; means for varying the relative flow rates of the laminar flows of fluids to vary the respective lateral extensions of the laminar flows over the sensing surface containing the sensing area or areas; and, detection means for detecting interaction events at the sensing area or areas. These flow cells are designed such that the sensing surface is a part of the wall surface within the flow cell. When the sensor is part of the flow cell wall, there is no way to route an optical fiber. Thus, the flow cell design does not allow incorporation of an optical fiber sensor.
Jorgenson et al. (U.S. Pat. Nos. 5,359,681; 5,647,030; and 5,835,645) disclose a fiber optic sensor which detects a sample in contact with the sensor by surface plasmon resonance (SPR) measurements. The sensor includes a surface plasmon supporting metal layer in contact with an exposed portion of the optical fiber core. Detection of a sample with the fiber optic SPR sensor is made, in part, by contacting the sample with the sensing area of the optical fiber. The sensing area is made by exposing a portion of the optical fiber core by removal of the surrounding cladding or cladding/buffer layers, and adhering an SPR supporting metal layer to the exposed optical fiber core. The SPR supporting metal layer of the optical fiber is then exposed to the sample of interest, and the refractive index of the sample is determined. The problem with this configuration is that it is difficult to keep the optical fiber straight while mass producing the flow cell with consistency. Moreover, the invention does not address a method for optimizing sampling.
An object of the present invention is to provide a flow cell that allows for various studies to be conducted on a sample or a variety of samples and sample combinations.
Another object of the invention is to provide a flow cell that employs a grating-based optical fiber sensor system.
Another object of the invention is to provide a flow cell that is capable of operation under varying flow rates with varying sample sizes.
Another object is to present a flow cell that permits measurement of reaction rates.
Another object of the invention is to provide a flow cell that is easy to manufacture and assemble with consistency.
Another object of the invention is to provide a flow cell that can be easily modified to achieve the desired testing apparatus.
Another object of the invention is to provide a flow cell design that provides the flexibility to increase the number of sample channels without compromising the ability of the sensors within the flow cell to make accurate measurements.